Cholestatic liver diseases

Abstract

Cholestatic liver diseases are rare diseases that affect hepatocytes and intrahepatic and/or extrahepatic bile ducts, causing interruptions in bile production or flow. Primary biliary cholangitis (PBC) is a new term for primary biliary cirrhosis. Immune-mediated attack leads to progressive destruction of small intralobular bile ducts and may lead to the development of fibrosis, cirrhosis and liver failure. Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation with damage and fibrosis of bile ducts, causing structuring and obliteration of the lumen. It can affect the intrahepatic and/or extrahepatic biliary tree. PBC mostly affects women, while PSC is more common in men. Fatigue, pruritus and jaundice represent the most common complaints of patients with cholestatic liver diseases. Both diseases are often diagnosed in early, asymptomatic phase, as part of the assessment of abnormal liver tests which demonstrate cholestatic pattern, with predominant elevation of the alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). Patients often have other concurrent autoimmune diseases. PBC is characterized by the presence of anti-mitochondrial antibodies (AMA), while cholangiography is the method of choice for the diagnosis of PSC. Complications can result from cholestasis, inflammatory (autoimmune) process, liver cirrhosis or cancer development. Ursodeoxycholic acid is the therapy of choice for PBC as it slows the disease progression. However, there is no proven treatment that significantly impacts the course of PSC. For both diseases management is aimed at treating symptoms and managing complications such as pruritus, malabsorption of fat and fat-soluble vitamins, or bile duct strictures. Increased incidence of malignant tumours requires ongoing monitoring and timely treatment in order to improve patient survival. Liver transplantation represents the treatment of choice in the advanced stage of both diseases.